Clinical tolerability and pharmacokinetics of Erigerontis hydroxybenzene injection: Results of a randomized phase I study in healthy Chinese volunteers

Ju, Wenzheng; Zhao, Yang; Liu, Fang; Wu, Ting; Zhang, Jun; Liu, Shijia; Zhou, Ling; Dai, Guoliang; Ning-ning, Xiong; Fang, Zheng

doi:10.1016/j.phymed.2014.11.014

Cited by 6 publications

(1 citation statement)

References 20 publications

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“…Interest in its versatile protective effects in cardiovascular and cerebral diseases has been growing over the last decade. [34][35][36][37][38][39][40] Scutellarin, the major flavonoid component extracted from Dengzhanxixin, is known to exhibit potent cardiovascular and neuronal effects. 41) However, since it was discovered that scutellarein, one of the main in vivo metabolites of scutellarein, has a higher bioavailability than scutellarein, 15) its pharmacological activities have attracted more attentions.…”

Section: Discussionmentioning

confidence: 99%

Delineation of Platelet Activation Pathway of Scutellarein Revealed Its Intracellular Target as Protein Kinase C

Tian

Chang

et al. 2016

Biological & Pharmaceutical Bulletin

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Erigeron breviscapus has been widely used in traditional Chinese medicine (TCM) and its total flavonoid component is commonly used to treat ischemic stroke, coronary heart disease, diabetes and hypertension. Scutellarin is the major ingredient of E. breviscapus and scutellarein is one of the main bioactive metabolites of scutellarin in vivo, but the latter's pharmacological activities have not been fully characterized. Provided evidence that could inhibit platelet aggregation, the effect of scutellarein on rat washed platelets and its underlying mechanisms were evaluated in our research. Scutellarein inhibited platelet adhesion and aggregation induced by multiple G protein coupled receptor agonists such as thrombin, U 46619 and ADP, in a concentration-dependent manner. Furthermore, the mild effect of scutellarein on intracellular Ca 2 mobilization and cyclic AMP (cAMP) level was observed. On the other hand, the role of scutellarein as potential protein kinase C (PKC) inhibitor was confirmed by PKC activity analysis and molecular docking. The phorbol myristate acetate-induced platelets aggregation assay with or without ADP implied that the scutellarein takes PKC(s) as its primary target(s), and acts on it in a reversible way. Finally, scutellarein as a promising agent exhibited a high inhibition effect on ADP-induced platelet aggregation among its analogues. This study clarifies the PKC-related signaling pathway involved in antiplatelet action of scutellarein, and may be beneficial for the treatment of cardiovascular diseases.

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Section: Discussionmentioning

confidence: 99%

Delineation of Platelet Activation Pathway of Scutellarein Revealed Its Intracellular Target as Protein Kinase C

Tian

Chang

et al. 2016

Biological & Pharmaceutical Bulletin

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β‐Glucuronidase‐ and OATP2B1‐mediated drug interaction of scutellarin in Dengzhan Xixin Injection: A formulation aspect

Shi

Sun

Huang

et al. 2020

Drug Development Research

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Scutellarin is the major and active constituent of Dengzhan Xixin Injection (DZXX), a traditional Chinese medicine prepared from the aqueous extract of Erigeron breviscapus and widely used for the treatment of various cerebrovascular diseases in clinic. In present study, the possible pharmacokinetic differences of scutellarin after intravenous administration of scutellarin alone or DZXX were explored. Additional, the potential roles of β‐glucuronidase (GLU) and OATP2B1 in drug–drug interaction (DDI) between scutellarin and constituents of DZXX were further evaluated in vitro. The plasma concentration, urinary and biliary excretion of scutellarin in rats after administration of DZXX, were significantly higher than those received scutellarin, while pharmacokinetic profile of Apigenin 7‐O‐glucuronide (AG) in rats was similar no matter AG or DZXX group. Furthermore, higher concentration in brain and plasma, however, lower level of scutellarin in intestine were observed after intravenous administration of DZXX. Finally, AG and caffeoylquinic acid esters were found to significantly inhibit GLU and OATP2B1 in vitro, which might explain, at least in part, the pharmacokinetic DDI between scutellarin and other chemical constituents in DZXX. The findings provided deep insight into the prescription‐formulating principle in DZXX for treating the cerebrovascular diseases.

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Endothelial Cells: From Dysfunction Mechanism to Pharmacological Effect in Cardiovascular Disease

et al. 2018

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Clinical tolerability and pharmacokinetics of Erigerontis hydroxybenzene injection: Results of a randomized phase I study in healthy Chinese volunteers

Cited by 6 publications

References 20 publications

Delineation of Platelet Activation Pathway of Scutellarein Revealed Its Intracellular Target as Protein Kinase C

Delineation of Platelet Activation Pathway of Scutellarein Revealed Its Intracellular Target as Protein Kinase C

β‐Glucuronidase‐ and OATP2B1‐mediated drug interaction of scutellarin in Dengzhan Xixin Injection: A formulation aspect

Endothelial Cells: From Dysfunction Mechanism to Pharmacological Effect in Cardiovascular Disease

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